Date of Award
2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Neuroscience
First Advisor
Sayamwong E. Hammack
Abstract
Anxiety disorders are among the most prevalent psychiatric disorders, effecting approximately one-third of the population during their lifetime and about 20% of the population annually. Chronic or severe stress can cause or exacerbate many psychiatric disorders, including anxiety disorders and post-traumatic stress disorder (PTSD). Therefore, understanding the underlying neurobiology of stress and anxiety behavior may be imperative for the prevention and treatment of these disorders. There is a long-standing literature suggesting that the bed nucleus of the stria terminalis (BNST) is implicated in anxiety-like behavior and serves as a nexus integrating both acute and chronic stressor exposure. Our lab has demonstrated an important role of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) in stress and emotional behavior. PACAP is increased in the BNST following chronic stressor exposure and PACAP receptor activation in the BNST is both necessary and sufficient to generate anxiety-like behavior. In addition to local PACAP producing neurons in the BNST, the primary source of BNST PACAP may be the lateral parabrachial nucleus (LPBn), which we have demonstrated by both lesioning and neuronal tracing studies. The purpose of this dissertation was to understand the role of PACAPergic LPBn terminals in the BNST in stress and anxiety-like responding. We found that LPBn neurons are activated following both acute and chronic stressor exposure and that a portion of those neuron project to the BNST. Moreover, PACAP mRNA transcripts are also upregulated in the LPBn following acute and chronic stressor exposure. These results suggest that this circuit may be important for transmitting information regarding stressful stimuli. Next, we examined if activation of PACAPergic LPBn afferents in the BNST could modulate anxiety-like behavior. We found that activation of this pathway dramatically increased anxiety-like behavior. Moreover, since PACAP LPBn neurons can also express other neuropeptides and transmitters, we found that BNST PAC1 receptor activation is necessary for the anxiety-like effects we observed. Lastly, we examined if inactivation of PACAPergic LPBn afferents in the BNST could prevent the anxiogenic effects of acute stressor exposure. Neither inactivation of this circuit post-stress but prior to behavior, nor prior to stress could prevent the anxiogenic effects of stress. Furthermore, inactivation prior to stress may be anxiogenic. Together the results of this dissertation suggest that PACAPergic LPBn afferents in the BNST have dynamic, yet complex, roles in stress and anxiety-like responding.
Language
en
Number of Pages
205 p.
Recommended Citation
Boucher, Melissa Nicole, "The Role Of A Pituitary Adenylate Cyclase-Activating Polypeptide (pacap) Circuit In Stress And Anxiety" (2023). Graduate College Dissertations and Theses. 1718.
https://scholarworks.uvm.edu/graddis/1718